CH243738A - Process for the preparation of a medicinal substance which is readily soluble in water. - Google Patents
Process for the preparation of a medicinal substance which is readily soluble in water.Info
- Publication number
- CH243738A CH243738A CH243738DA CH243738A CH 243738 A CH243738 A CH 243738A CH 243738D A CH243738D A CH 243738DA CH 243738 A CH243738 A CH 243738A
- Authority
- CH
- Switzerland
- Prior art keywords
- water
- triazine
- preparation
- phosphoric acid
- readily soluble
- Prior art date
Links
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 title claims description 6
- 238000000034 method Methods 0.000 title claims description 5
- 238000002360 preparation method Methods 0.000 title claims description 3
- 239000012907 medicinal substance Substances 0.000 title description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 12
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 claims description 8
- 230000001882 diuretic effect Effects 0.000 claims description 5
- 229910052698 phosphorus Inorganic materials 0.000 claims description 4
- 150000003839 salts Chemical class 0.000 claims description 4
- 150000001875 compounds Chemical class 0.000 claims description 3
- 239000002934 diuretic Substances 0.000 claims description 3
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims description 2
- 230000007062 hydrolysis Effects 0.000 claims description 2
- 238000006460 hydrolysis reaction Methods 0.000 claims description 2
- 239000000155 melt Substances 0.000 claims description 2
- 239000003960 organic solvent Substances 0.000 claims description 2
- 125000004437 phosphorous atom Chemical group 0.000 claims description 2
- 239000011574 phosphorus Substances 0.000 claims description 2
- 239000003814 drug Substances 0.000 claims 1
- 229940079593 drug Drugs 0.000 claims 1
- 239000000843 powder Substances 0.000 claims 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- OFAPSLLQSSHRSQ-UHFFFAOYSA-N 1H-triazine-2,4-diamine Chemical compound NN1NC=CC(N)=N1 OFAPSLLQSSHRSQ-UHFFFAOYSA-N 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 208000004880 Polyuria Diseases 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 150000003918 triazines Chemical class 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6515—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having three nitrogen atoms as the only ring hetero atoms
- C07F9/6521—Six-membered rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
Verfahren zur Darstellung eines in Wasser gut löslichen Arzneistoffes. Es wurde gefunden, dass das bekannte 2,4-Diamino-triazin-(1,3,5) diuretische Wir kung besitzt. Der medizinischen Verwendung steht jedoch seine Schwerlöslichkeit hinder lich im Wege. Es taugt weder für Injektionen noch kommt seine diuretische Wirkung bei oraler Verabreichung in ausreichendem Masse zur Geltung.
Es wurde ferner gefunden, dass man durch Überführung des 2,4-Diamino- triazins-(1,3,5) in das 2,4-Di-(phosphorsäure- monoamino)-triazin-(1,3,5) von der Formel
EMI0001.0013
zu einem ausgezeichneten Diuretikum gelangt, welches in Wasser leicht löslich ist und mit Basen leicht lösliche Salze bildet.
Das Verfahren zur Darstellung der neuen Verbindung ist dadurch gekennzeichnet, dass man 2,4-Diamino-triazin-(1,3,5) mit einer Verbindung des 5wertigen Phosphors, deren Phosphoratom mit mindestens 3 Halogen atomen direkt verbunden ist, und die durch Hydrolyse in o-Phosphorsäure übergeht, umsetzt und das dabei erhaltene Produkt zum 2,4-Di-(phosphorsäuremonoamino)-triazin- (1,3,5) hydrolysiert. Als Phosphorverbindun gen können z.
B. Phosphoroxychlorid oder Phosphorpentachlorid verwendet werden. Ausführungsbeispiel: Eine Mischung von 10 g 2,4-Diamino- triazin-(1,3,5) und 150 g Phosphoroxycblorid wird 12 Stunden am Rückflusskühler gekocht. Das überschüssige Phosphoroxychlorid wird im Vakuum abdestilliert, der Rückstand mit Chloroform verrieben, abgenutscht und mit Chloroform ausgewaschen.
Das so erhaltene 2,4-Di-(phosphor säuredichloridmonoamino)-tri- azin-(1,3,5) wird getrocknet, mit 30g Natrium bikarbonat gemischt und der Ifischung so viel Eis zugefügt, als zur hydrolytischen Entfer nung der Chloratome eben nötig ist. Nach Beendigung der Kohlendioxydentwicklung wird das 2,4-Di-(phosphorsäuremonoamino)-triazin- (1,3,5) durch Zugabe von 100 cm' Äthanol ausgefällt.
Es wird gesammelt, zur weiteren Reinigung noch feucht mit 500 cm' Äthanol ausgekocht und warm abgenutscht. Ausbeute 16 g, entsprechend 64/o d. Th. Das gebildete Triazin-Derivat lässt sich auch in Form seiner Salze, z. B. des Natriiuns oder Calciums, isolieren.
Das 2,4-Di-(phosphorsäuremonoamino)- triazin-(1,3,5) ist ein farbloses, in Wasser sehr leicht lösliches, in den gebräuchlichen organischen Lösungsmitteln unlösliches Pul ver, welches bei schnellem Erhitzen zwischen 250 . und<B>260'</B> schmilzt. Es soll als solches oder in Form seiner Salze therapeutisch, insbesondere als Diuretikum verwendet wer den.
Process for the preparation of a medicinal substance which is readily soluble in water. It has been found that the known 2,4-diamino-triazine (1,3,5) diuretic effect has. However, its poor solubility stands in the way of medical use. It is neither suitable for injections nor is its diuretic effect sufficiently effective when administered orally.
It was also found that by converting the 2,4-diamino-triazine- (1,3,5) into the 2,4-di- (phosphoric acid monoamino) -triazine- (1,3,5) of the formula
EMI0001.0013
comes to an excellent diuretic, which is easily soluble in water and forms easily soluble salts with bases.
The process for preparing the new compound is characterized in that 2,4-diamino-triazine- (1,3,5) with a compound of pentavalent phosphorus, whose phosphorus atom is directly connected to at least 3 halogen atoms, and which by hydrolysis passes into o-phosphoric acid, reacted and the product obtained thereby hydrolyzed to 2,4-di- (phosphoric acid monoamino) -triazine- (1,3,5). As Phosphorverbindun conditions can, for.
B. phosphorus oxychloride or phosphorus pentachloride can be used. Exemplary embodiment: A mixture of 10 g of 2,4-diaminotriazine (1,3,5) and 150 g of phosphorus oxychloride is refluxed for 12 hours. The excess phosphorus oxychloride is distilled off in vacuo, the residue triturated with chloroform, suction filtered and washed out with chloroform.
The 2,4-di- (phosphoric acid dichloride monoamino) -triazine- (1,3,5) obtained in this way is dried, mixed with 30g sodium bicarbonate and as much ice is added to the mixture as is necessary for the hydrolytic removal of the chlorine atoms is. When the evolution of carbon dioxide has ceased, the 2,4-di- (phosphoric acid monoamino) -triazine- (1,3,5) is precipitated by adding 100 cm of ethanol.
It is collected, boiled while still moist with 500 cm of ethanol for further cleaning and sucked off warm. Yield 16 g, corresponding to 64 / o d. Th. The triazine derivative formed can also be used in the form of its salts, e.g. B. of sodium or calcium isolate.
The 2,4-di- (phosphoric acid monoamino) - triazine- (1,3,5) is a colorless, very easily soluble in water, insoluble in the common organic solvents, which with rapid heating between 250. and <B> 260 '</B> melts. It should be used as such or in the form of its salts therapeutically, in particular as a diuretic who the.
Claims (1)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH243738T | 1945-10-15 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH243738A true CH243738A (en) | 1946-07-31 |
Family
ID=4463774
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH243738D CH243738A (en) | 1945-10-15 | 1945-10-15 | Process for the preparation of a medicinal substance which is readily soluble in water. |
Country Status (1)
| Country | Link |
|---|---|
| CH (1) | CH243738A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1301819B (en) * | 1962-08-01 | 1969-08-28 | Degussa | Substituted 2,4-diamino-6-chloro-s-triazines |
-
1945
- 1945-10-15 CH CH243738D patent/CH243738A/en unknown
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1301819B (en) * | 1962-08-01 | 1969-08-28 | Degussa | Substituted 2,4-diamino-6-chloro-s-triazines |
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